Interest of a loading dose of milnacipran in endogenous depressive inpatients

Ansseau, M; Frenckell, Remy R. von; Gérard, Marie Anne; Mertens, C; Wilde, Jules J. De; Botte, L.; Devoitille, Jean Michel J.M.; Evrard, Jean-Luc; Nayer, André; Darimont, Philippe; Mirel, J; Troisfontaines, B.; Toussaint, C; Couzinier, Jean‐Pierre; Demarez, Jean-Paul; Serre, C.

doi:10.1016/0924-977x(91)90712-4

Cited by 22 publications

(31 citation statements)

References 20 publications

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“…In clinical trials with depressed patients, milnacipran (50 mg twice daily) has been shown to have significant antidepressant activity compared with placebo [5, 6]. It has also been shown to be at least as efficacious as typical tricyclic antidepressants (TCAs) [7, 8] and the selective serotonin reuptake inhibitors (SSRIs), fluvoxamine and fluoxetine [9, 10].…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamics of milnacipran in young and elderly volunteers

Hindmarch

Rigney

Stanley

et al. 2000

Brit J Clinical Pharma

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Aims To investigate the pharmacodynamics of milnacipran in healthy young and elderly volunteers. Methods Randomized double-blind crossover designs were employed and a standardized psychometric battery was administered pre and post dose for both studies. In the first study 10 healthy young volunteers received milnacipran 12.5 mg, 25 mg, 50 mg, 100 mg as a single dose or matched placebo. The test battery was administered at baseline and at 1, 2, 4 and 6 h post dose. The second study compared the effects of milnacipran 75 mg (50 mg+25 mg) per day, amitriptyline 50 mg (25 mg+25 mg) per day and placebo for 3 days' dosing in healthy volunteers aged over 65 years. The test battery was administered at baseline and at 2, 10 and 24 h post dose. The psychometric battery included critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking (CTT) and tests of short-term memory (STM), subjective sedation (LARS) and subjective sleep (LSEQ). Results Milnacipran produced no significant dose related effects in the young volunteers. For the elderly, milnacipran significantly ( P<0.05) raised CFF scores compared with placebo but had no significant effects on any of the other measures used. Amitriptyline, in contrast, significantly ( P<0.05) lowered CFF threshold, lengthened CRT and increased error on the CTT. On the subjective variables, LARS and LSEQ, amitriptyline increased ratings both of sedation and of difficulty in waking from sleep. Conclusions The results showed that milnacipran at single doses of up to 100 mg in healthy young volunteers is free from disruptive effects on cognitive function and psychomotor performance. In addition, milnacipran 75 mg (50+25 mg) appears to be free of negative effects on cognitive function in elderly volunteers, where it seemingly improves performance on CFF. In contrast, the tricyclic antidepressant amitriptyline, used here as a positive internal control, significantly impaired performance in the elderly on the majority of psychometric measures used in this study. This finding not only validated the sensitivity of this current test battery but also indicates the potential behavioural toxicity of amitriptyline in clinical use in the elderly.

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Section: Introductionmentioning

confidence: 99%

Pharmacodynamics of milnacipran in young and elderly volunteers

Hindmarch

Rigney

Stanley

et al. 2000

Brit J Clinical Pharma

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“…In view of the half-life of milnacipran (7–8 hours) this protocol was inappropriate given that twice daily dosing of milnacipran is recommended. In two studies,39,40 each comparing two doses of milnacipran with a single dose of a SSRI, the meta-analysis inappropriately compared each dose of milnacipran with the SSRI, using the single SSRI group twice, thus giving excessive importance to the SSRI groups. Most importantly, however, the analysis combined, without distinction, data from a study in severely depressed hospitalized patients33 (baseline HDRS > 32) with data from studies in mildly depressed outpatients32,41 (baseline HDRS < 24).…”

Section: Comparison Of Milnacipran With Tcas and Ssrismentioning

confidence: 99%

Milnacipran: a unique antidepressant?

Kasper

Pail²

2010

NDT

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Tricyclic antidepressants (TCAs) are among the most effective antidepressants available, although their poor tolerance at usual recommended doses and toxicity in overdose make them difficult to use. While selective serotonin reuptake inhibitors (SSRIs) are better tolerated than TCAs, they have their own specific problems, such as the aggravation of sexual dysfunction, interaction with coadministered drugs, and for many, a discontinuation syndrome. In addition, some of them appear to be less effective than TCAs in more severely depressed patients. Increasing evidence of the importance of norepinephrine in the etiology of depression has led to the development of a new generation of antidepressants, the serotonin and norepinephrine reuptake inhibitors (SNRIs). Milnacipran, one of the pioneer SNRIs, was designed from theoretic considerations to be more effective than SSRIs and better tolerated than TCAs, and with a simple pharmacokinetic profile. Milnacipran has the most balanced potency ratio for reuptake inhibition of the two neurotransmitters compared with other SNRIs (1:1.6 for milnacipran, 1:10 for duloxetine, and 1:30 for venlafaxine), and in some studies milnacipran has been shown to inhibit norepinephrine uptake with greater potency than serotonin (2.2:1). Clinical studies have shown that milnacipran has efficacy comparable with the TCAs and is superior to SSRIs in severe depression. In addition, milnacipran is well tolerated, with a low potential for pharmacokinetic drug–drug interactions. Milnacipran is a first-line therapy suitable for most depressed patients. It is frequently successful when other treatments fail for reasons of efficacy or tolerability.

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“…In studies carried out in Europe and the US, the antidepressant effect of milnacipran has been shown to be superior to placebo 3. Further, the antidepressant effect and tolerability have been shown to be comparable or superior to comparators, such as selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine, paroxetine),4–8 a serotonin-norepinephrine reuptake inhibitor (venlafaxine),9 and tricyclic antidepressants (amitriptyline, imipramine) 10–13. However, no study has been conducted in Japan with the aim of confirming the noninferiority of milnacipran to previously introduced drugs using a fixed-dose scheme.…”

Section: Introductionmentioning

confidence: 99%

Double-blind, comparative study of milnacipran and paroxetine in Japanese patients with major depression

Kamijima

Hashimoto²,

Nagayoshi³

et al. 2013

NDT

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Background and methodsA double-blind, parallel-group, controlled study was performed to investigate if milnacipran was noninferior to paroxetine in terms of improvement in symptoms of depression in Japanese patients with major depressive disorders in a fixed-dose design. The efficacy and safety of milnacipran 200 mg/day were also assessed in comparison with those at the standard dose of 100 mg/day.ResultsChanges in 17-item Hamilton depression rating scale (HAM-D) total score (mean ± standard deviation) for group M1 (milnacipran 100 mg/day), group M2 (milnacipran 200 mg/day), and group PX (paroxetine 30 or 40 mg/day) were −12.9 ± 5.8, −12.8 ± 6.1, and −13.1 ± 6.2, respectively, and the estimated differences in total score for group PX (Dunnett’s 95% simultaneous confidence interval) were 0.1 (−1.1 to 1.3) for group M1 and 0.3 (−0.9 to 1.5) for group M2. The noninferiority of groups M1 and M2 to group PX was thus confirmed, because the upper confidence limit of differences between groups M1 and PX and between groups M2 and PX was less than 2.0. The estimated mean difference of change in HAM-D total score (95% confidence interval) between groups M2 and M1 was 0.2 (−0.9 to 1.2), indicating a comparable change in total score for both groups. The incidence of treatment-related adverse events was 71.7% for group M1, 68.8% for group M2, and 69.3% for group PX, indicating no significant difference between the three groups.ConclusionThese results demonstrate that milnacipran 100 mg/day and 200 mg/day is not inferior to paroxetine in terms of efficacy and safety.

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Interest of a loading dose of milnacipran in endogenous depressive inpatients

Cited by 22 publications

References 20 publications

Pharmacodynamics of milnacipran in young and elderly volunteers

Pharmacodynamics of milnacipran in young and elderly volunteers

Milnacipran: a unique antidepressant?

Double-blind, comparative study of milnacipran and paroxetine in Japanese patients with major depression

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